Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Hemicranial volume deficits in patients with temporal lobe epilepsy with and without hippocampal sclerosis

PURPOSE: In patients with refractory temporal lobe epilepsy, studies have suggested volume deficits measured by MRI of brain structures outside the epileptogenic hippocampus. Hippocampal sclerosis (HS) is a frequent, but not obligate, finding in such patients. The present study examines the influence of the presence of HS on quantitative magnetic resonance imaging (MRI) measurements. METHODS: We analyzed 47 patients and 30 controls by quantitative MRI, including intracranial volume (ICV), hemicranial volume, hippocampal volume (HCV), and T2 relaxometry. MRI results were compared with histological findings in the resected temporal lobe. RESULTS: Histology documented HS in 35 patients (HS group) and other findings in 12 patients (no-HS group). In both groups, the hemicranial volume ipsilateral to the epileptogenic focus was significantly smaller than on the contralateral side (p < 0.004). The HCV on both sides was smaller in the HS group compared with patients without HS (p < or = 0.004). Unilateral hippocampal atrophy and increased T2 value were found in 71% of patients with HS, and bilaterally normal HCV and T2 value were found in 67% of patients without HS. CONCLUSIONS: The smaller hemicranial volume on the focus side, irrespective of the presence or absence of HS suggests a different pathogenic mechanism for the additional hemicranial volume deficit, compared to HS itself. The contralateral HCV deficit depends on the presence of HS, indicating a pathogenic connection between damage to both hippocampi.     

Corpora amylacea in hippocampal sclerosis

Corpora amylacea have been reported in around 60% of hippocampal sclerosis specimens. The aim was to determine whether there are clinical and quantitative hippocampal MRI differences between hippocampal sclerosis with and without corpora amylacea. Corpora amylacea density was determined in 46 resected hippocampi of patients with temporal lobe epilepsy, using a three dimensional microscopical counting technique. Forty one hippocampi had hippocampal sclerosis. Twenty six of the 41 (63%) hippocampal sclerosis specimens contained corpora amylacea, which were found in highest numbers in the CA1 subregion of the hippocampus. Corpora amylacea density in the CA1 correlated inversely with the neuronal density in CA1. Hippocampal sclerosis with corpora amylacea had the same clinical and quantitative hippocampal MRI characteristics as hippocampal sclerosis without corpora amylacea, and did not affect seizure outcome after surgery adversely. In conclusion, formation of corpora amylacea seems to be a pathological response to neuronal cell loss in most hippocampal sclerosis specimens, with no clear clinical and quantitative hippocampal MRI correlates.     

Clinical correlations with hippocampal atrophy

There is now a consensus that magnetic resonance imaging (MRI) is a sensitive and specific indicator of mesial temporal sclerosis (MTS) in patients with partial epilepsy. MTS is the most common pathological finding underlying the epileptogenic zone in patients undergoing temporal lobe surgery for medically refractory partial seizures. MRI-based hippocampal volumetric studies (i.e., quantitative MRI), has been shown to provide objective evidence for hippocampal atrophy in patients with MTS. The hippocampal volume in the epileptic temporal lobe has correlated with the neuronal cell densities in selected hippocampal subfields. A history of febrile seizures in childhood and age of unprovoked seizure onset have been associated with MRI-based hippocampal volumetry. There is conflicting evidence regarding the relationship between the duration of the seizure disorder and volumetry. Quantitative MRI has compared favorably to other noninvasive techniques (e.g., scalp-recorded EEG), in indicating the diagnosis of medical temporal lobe epilepsy (MTLE). MRI-identified hippocampal atrophy has also been a favorable prognostic indicator of seizure outcome after temporal lobe surgery. The presence of hippocampal atrophy appears to serve an in vivo surrogate for the presence of MTS.     

Memory for Visuospatial Location Following Selective Hippocampal Sclerosis: The Use of Different Coordinate Systems.

This study addressed the role of the medial temporal lobe regions and, more specifically, the contribution of the human hippocampus in memory for body-centered (egocentric) and environment-centered (allocentric) spatial location. Twenty-one patients with unilateral atrophy of the hippocampus secondary to long-standing epilepsy (left, n = 7; right, n = 14) and 15 normal control participants underwent 3 tasks measuring recall of egocentric or allocentric spatial location. Patients with left hippocampal sclerosis were consistently impaired in the allocentric conditions of all 3 tasks but not in the egocentric conditions. Patients with right hippocampal sclerosis were impaired to a lesser extent and in only 2 of the 3 tasks. It was concluded that hippocampal structures are crucial for allocentric, but not egocentric, spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacokinetics and systemic effect on calcium homeostasis of 1 alpha,24-dihydroxyvitamin D2 in rats. Comparison with 1 alpha,25-dihydroxyvitamin D2, calcitriol, and calcipotriol

The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.     

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.     

Hippocampal sclerosis revisited

Studies dating back more than 150 years reported a relationship between hippocampal sclerosis and epilepsy. Retrospective studies of patients who underwent temporal lobectomy for intractable partial epilepsy found a relationship between a history of early childhood convulsions, hippocampal sclerosis, and the development of temporal lobe epilepsy. Many believe that febrile seizures lead to hippocampal damage and this in turn predisposes the patient to the development of temporal lobe epilepsy. Studies in adult rats have shown that seizures can lead to hippocampal damage and unprovoked recurrent seizures. However, many questions remain as to the relevance of early childhood seizures to hippocampal sclerosis and temporal lobe epilepsy. Human prospective epidemiologic studies have not shown a relationship between early childhood seizures and temporal lobe epilepsy. Recent MRI studies in humans suggest that a preexisting hippocampal lesion may predispose infants to experience febrile seizures, later on hippocampal sclerosis, and possibly temporal lobe epilepsy may occur. Unlike the studies in adult rats, normal immature rats with seizures have not been shown to develop hippocampal damage or unprovoked seizures in adulthood. Furthermore, animal studies reveal that preexisting brain abnormalities can predispose to hippocampal damage following seizures early in life. This paper reviews evidence for and against the view that early childhood convulsions, hippocampal sclerosis, and temporal lobe epilepsy are related, while also exploring clinical and animal studies on how seizures can lead to hippocampal damage, and how this can result in temporal lobe epilepsy. By better understanding the cause and effect relationship between early childhood seizures and hippocampal injury in normal and abnormal brains specific treatments can be developed that target the pathogenesis of epilepsy.     

Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study

OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58% of the 50 patients. This appearance was observed in 64% of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.     

Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings

Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.     

Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy

The goals of this study were to determine (1) the yield of magnetoencephalography (MEG) according to epilepsy type, (2) if MEG spike sources colocalize with focal epileptogenic pathology, and (3) if MEG can identify the epileptogenic zone when scalp ictal electroencephalogram (EEG) or magnetic resonance imaging (MRI) fail to localize it. Twenty-two patients with mesial temporal (10 patients), neocortical temporal (3 patients), and extratemporal lobe epilepsy (9 patients) were studied. A 37-channel biomagnetometer was used for simultaneously recording MEG with EEG. During the typical 2-3-hour MEG recording session, interictal epileptiform activity was observed in 16 of 22 patients. MEG localization yield was greater in patients with neocortical epilepsy (92%) than in those with mesial temporal lobe epilepsy (50%). In 5 of 6 patients with focal epileptogenic pathology, MEG spike sources were colocalized with the lesions. In 11 of 12 patients with nonlocalizing (ambiguous abnormalities or normal) MRI, MEG spike sources were localized in the region of the epileptogenic zone as ultimately defined by all clinical and EEG information (including intracranial EEG). In conclusion, MEG can reliably localize sources of spike discharges in patients with temporal and extratemporal lobe epilepsy. MEG sometimes provides noninvasive localization data that are not otherwise available with MRI or conventional scalp ictal EEG.     

FDG-PET and volumetric MRI in the evaluation of patients with partial epilepsy

We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.     

Significance of interictal temporal lobe delta activity for localization of the primary epileptogenic region

Because interictal temporal lobe delta activity (TLDA) has been described in 30 to 90% of patients with temporal lobe epilepsy (TLE) but has not been investigated in patients with extratemporal epilepsy, we sought to determine the localizing significance of TLDA. We compared the presurgical interictal scalp EEG results of 47 consecutive patients who received extratemporal resection (40 frontal and 7 parietal-occipital) for intractable epilepsy with 43 consecutive patients who received anterior temporal lobectomy. We defined lateralized TLDA as runs of lower than 4-Hz waveforms that were easily distinguished from the background rhythms and were maximal at electrodes T4, F8, and T6 or T3, F7, and T5. The lateralized TLDA was subcategorized as temporal intermittent rhythmic delta activity (TIRDA) or temporal intermittent polymorphic delta activity (TIPDA). A chi-square test was used to determine the association of the lobe of the epileptogenic zone with TIRDA and TIPDA. We found TIRDA in 12 (28%) and TIPDA in 8 (19%) patients in the temporal lobe group, and TIRDA in 2 (4%) and TIPDA in 9 (19%) patients in the extratemporal group. TIRDA was strongly associated with TLE (p < 0.003), whereas TIPDA occurred at an equal rate in both groups. Similar to anterior temporal epilepsy, lateralized TIPDA is present in up to 20% of patients with extratemporal epilepsy. The presence of TIRDA strongly suggests TLE but may infrequently occur in extratemporal epilepsy. Caution should be used when using lateralized TLDA as a presurgical localizing finding.     

Incidence of lesions described by magnetic resonance imaging in the clarification of focal epilepsy of frontal and temporal origin

AIM: Today, MRI is an integral part of the presurgical evaluation of patients suffering from partial epilepsy. These patients frequently show focal morphological abnormalities with potential epileptogenic character and surgical resection of these lesions is associated with superior postsurgical outcome as to seizure frequency. Apart from easily detectable defects, such as post-traumatic lesions or cerebral infarction, as wide variety of mainly small abnormalities can be detected using MRI. METHODS: In this study, 484 patients suffering from partial epilepsy of temporal or frontal onset were evaluated for the incidence of different lesions in this population. RESULTS: All lesions found were included without evaluating their potential epileptogenicity, which remains to be proven using other procedures (EEG, SPECT, PET, etc.). Involvement of the hippocampal formation was a major finding in temporal lobe epilepsy, which could be detected as sclerosis (T2w-images), atrophy (T2w-TSE or T1w-IR-images) or both (15%). In addition and in declining frequency various tumors (14%), post-traumatic lesion (-5%), and focal cortical dysplasia or other disturbances of cortical integrity (-4%) were found. These lesions are detectable with best contrast on different sequences. As a consequence it is suggested to acquire sequences in 3 dimensions including a T1w-SE, two (coronal and axial) double-echo-SE sequences and similarly two T1w-IR-sequences. The application of contrast media can be restricted to special questions, derived either from the first imaging results or from the patients history. CONCLUSION: Using qualitative data for interpretation, the sensitivity as to the detection of any focal pathology of a recent-generation MRI in this population was 75%, with 79% for temporal lobe epilepsies and 67% for frontal lobe epilepsies. Quantitative measurements of hippocampal volume or signal seem to be able to increase the sensitivity of the method.     

Quantitative MRI in outpatient childhood epilepsy

PURPOSE: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. METHODS: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. RESULTS: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. CONCLUSIONS: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.     

In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis

By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography. We applied a magnetic resonance imaging-based method for partial volume effect correction to the PET images of [11C]FMZ volume of distribution ([11C]FMZ Vd) obtained in 10 patients with refractory mTLE due to unilateral, histologically verified HS. Saturation autoradiography was performed on the hippocampal specimens obtained from the same patients, allowing calculation of receptor availability ([3H]FMZ Bmax). After correction for partial volume effect, [11C]FMZ Vd in the body of the epileptogenic hippocampus was reduced by a mean of 42.1% compared with normal controls. [3H]FMZ Bmax, determined autoradiographically from the same hippocampal tissue, was reduced by a mean of 42.7% compared with control hippocampi. Absolute in vivo and ex vivo measurements of cBZR binding for the body of the hippocampus were significantly correlated in each individual. Our study demonstrates that reduction of available cBZR on remaining neurons in HS can be reliably detected in vivo by using [11C]FMZ-PET after correction for partial volume effect.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.     

Octreotide: effective treatment for hyperparathyroidism? A prospective, randomized, controlled clinical trial

Although clinical and electrophysiological evidence indicates that the amygdaloid body plays an important role in the pathogenesis of temporal lobe epilepsy, there are very few detailed data on histopathological changes in this nucleus in epilepsy patients. In the present study we have examined the lateral nucleus of the amygdaloid body in 70 surgical specimens from patients with temporal lobe epilepsy and in 10 control specimens with respect to neuronal density and gliosis. The results were compared to the neuronal loss in the hippocampal formation. Our goal was to examine the pathological alterations of the amygdaloid body and their correlation with other morphological changes in temporal lobe epilepsy. In epilepsy patients with Ammon's horn sclerosis or focal lesions of the temporal lobe, the neuronal density of the lateral amygdaloid nucleus was significantly decreased as compared to normal controls (P < 0.001). Overall, the mean volumetric density in epilepsy patients was reduced to 59% of that in normal individuals. There was no correlation between the neuronal density in the lateral amygdaloid nucleus and that in the different segments of the hippocampal formation or to the age at onset or the duration of epilepsy. The neuronal loss of the amygdaloid nucleus correlated well with the presence of fibrillary gliosis. Our findings demonstrate that the amygdaloid body is severely altered in most patients with temporal lobe epilepsy and that these changes are independent of those in the hippocampus. The presence of neuronal loss and gliosis in the amygdaloid nucleus of patients with focal lesions but no Ammon's horn sclerosis is compatible with an involvement of the amygdala in secondary epileptogenesis.     

Limbic system abnormalities associated with mesial temporal sclerosis: a model of chronic cerebral changes due to seizures

In a landmark 1966 study, widespread cerebral abnormalities were discovered at histopathologic examination of autopsied brains from patients with long-standing temporal lobe epilepsy. In the brains diagnosed with mesial temporal sclerosis (MTS), these abnormalities involved not only the hippocampus but also other structures of the limbic system and medial temporal lobe. Many of these changes are evident at magnetic resonance imaging. Because many of these abnormalities are found within limbic structures along a known neuroanatomic pathway (the Papez circuit), they suggest a pattern of cerebral damage related to the physiologic interconnections between the hippocampus and associated limbic structures. It appears that limbic damage associated with MTS more often affects the structures most closely connected to the hippocampus along the Papez circuit. The frequency and widespread distribution of these cerebral abnormalities suggest that MTS is not limited to the medial temporal lobe but instead represents a limbic system disorder.